Cystic fibrosis is the most common autosomal recessive disease among Caucasians, occurring once in every 1600-2500 live births. CF causes tremendous morbidity and early mortality and due to the frequent occurrence of the disease is a major public health problem. There is, therefore, a great need to better understand the basic biochemical defect in cystic fibrosis in order to enhance our efforts at diagnosing, treating, or preventing this disease. In our initial work we had shown that cystic fibrosis fibroblasts are resistant to killing by ouabain. We have expanded this work to show that CF cells are also resistant to the cytotoxic effects of steroid hormones as well as cAMP. We are currently studying the metabolic pathways for each of these types of drugs in normal and cystic fibrosis cells with the aim of identifying the specific biochemical defect in this condition. In addition, we are using the phenotype of drug resistance in CF cells to explore the possibilities of carrier detection for cystic fibrosis as well as the possibility of prenatal diagnosis for this disease. Our work therefore offers a new type of in vitro system for the study of the defect in cystic fibrosis and may even lead to a possible means of preventing this extremely common genetic disorder.